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Epithelial-Mesenchymal Transition-Related MicroRNAs and Their Target Genes in Colorectal Cancerogenesis

机译:上皮-间充质转化相关的微小RNA及其靶基因在大肠癌发生中的作用

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摘要

MicroRNAs of the family have been shown experimentally to regulate epithelial-mesenchymal transition (EMT). Although EMT is the postulated mechanism of development and progression of colorectal cancer (CRC), there are still limited and controversial data on expression of family and their target genes during CRC cancerogenesis. Our study included formalin-fixed paraffin-embedded biopsy samples of 40 patients (10 adenomas and 30 cases of CRC with corresponding normal mucosa). Expression of , and and their target genes ( , , , , , and ) was analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using immunohistochemistry. All miRNAs were down-regulated and their target genes showed the opposite expression in CRC compared to adenoma. Down-regulation of the family at the invasive front in comparison to the central part of tumour was observed as well as a correlation of expression of , , and expression to nodal metastases. Expression of the family and also correlated with E-cadherin staining. These results suggest that the family and their target genes contribute to progression of adenoma to CRC, invasive properties and development of metastases. Our results strongly support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC cancerogenesis.
机译:该家族的MicroRNA已通过实验证明可调节上皮-间质转化(EMT)。尽管EMT是结直肠癌(CRC)发生和发展的假定机制,但在CRC癌变过程中有关家族及其靶基因表达的数据仍然有限且有争议。我们的研究包括40例福尔马林固定石蜡包埋的活检样本(10例腺瘤和30例CRC,相应的正常黏膜)。使用定量实时PCR分析和及其靶基因(,,,,和)的表达。使用免疫组织化学分析E-钙粘着蛋白的表达。与腺瘤相比,所有miRNA均下调,其靶基因在CRC中显示相反的表达。与肿瘤的中心部分相比,观察到侵入家族中家族的下调,以及,和表达与淋巴结转移的相关性。该家族的表达也与E-钙粘蛋白染色相关。这些结果表明该家族及其靶基因有助于腺瘤发展为CRC,侵袭性和转移的发展。我们的结果有力地支持了CRC致癌过程中部分EMT和肿瘤内异质性的假说。

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